POS0321 LYMPHOCYTE SUBSETS- AND ACPA-BASED PREDICTIVE MODEL FOR PROGRESSION TO CLINICAL ARTHRITIS IN AT-RISK INDIVIDUALS WITH ARTHRALGIA
Authors: K. Prajzlerová, O. Kryštůfková, N. Kaspříková, N. Růžičková, H. Hulejova, P. Hánová, J. Vencovský, L. Šenolt, M. Filková
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The presence of antibodies against citrullinated proteins (ACPA) significantly increases the risk of developing rheumatoid arthritis (RA). The clinical definition of individuals with arthralgia at risk of progression to RA (clinically suspect arthralgia, CSA) was established by EULAR irrespective of the ACPA status. Dysregulation of lymphocyte subpopulations (including NK and B cells) was previously described in early and established RA. <h3>Objectives</h3> To propose the predictive model for progression to arthritis based on peripheral lymphocyte subsets and ACPA in at-risk individuals with arthralgia. <h3>Methods</h3> Individuals from the At Risk of RA (ARRA) prospective observational cohort were defined as having arthralgia without arthritis on the examination of 66 joints at baseline and being either ACPA+ and/or meeting the EULAR definition of CSA (further CSA+, fulfilling at least 3 out of 7 parameters). All individuals signed informed consent prior to study enrolment. Peripheral blood samples were analysed at baseline by flow cytometry. The percentage of CD19+ B cells, CD3+ T cells, CD3+CD4+ Th cells, CD3+CD8+ Tc cells, CD3-CD16/56+ NK cells, CD3+CD16/56+ NK-T cells, and CD3bright γδ-T cells were detected within the CD45+CD14- lymphocyte population. Robust ANOVA was used to evaluate the effect of ACPA positivity or the CSA definition. A logistic regression model with a baseline percentage of lymphocyte subpopulations as predictors was constructed to discriminate between progressors to arthritis and non-progressors. The preselection of the best subset of predictors was performed using a stepwise selection based on the Akaike Information Criterion. The models considered were evaluated using ROC curves. <h3>Results</h3> Out of 191 at-risk individuals, 36 developed clinical arthritis (progressors) within a median of 9 months of follow-up and with a median symptom duration of 31,65 months [IQR=44,25], CRP 5,30 mg/l [IQR=12,21] and DAS28(CRP) 4,62 [IQR=2,18] at the time of manifestation. Progressors included 39% ACPA+, 25% CSA+, and 36% both ACPA+ and CSA+ individuals. For the construction of predictive models, 81 individuals (median age 51 years [IQR=17], 89% females) who have not yet progressed to arthritis (non-progressors) with symptom duration longer than 12 months were included to avoid disqualification of non-progressors limited by CSA definition (symptom duration &lt;12 months). Forty-seven % of them were ACPA+, 36% were CSA+, and 17% were ACPA+ and CSA+, with median symptom duration at baseline being 36 months [IQR=36] and median CRP 1,64 mg/l [IQR=3,28]. No statistically significant differences in lymphocyte subpopulations between ACPA+ and ACPA- or CSA+ and CSA- individuals were found. The resulting predictive model for arthritis development performed in all ARRA individuals based on CD19%, NK%, and anti-CCP IgG U/ml showed AUC=0.732 (p&lt;0.001). According to this model, a high percentage of CD19+ B lymphocytes and high anti-CCP IgG levels, and a low percentage of NK cells increase the probability of developing clinical arthritis. When the model with the same set of predictors was applied to ACPA+ individuals, AUC was even higher (AUC=0.804; p&lt;0.0001). However, we were not able to construct a well-performing classification model in ACPA- individuals. The CSA definition appears of no predictive value in our at-risk cohort. <h3>Conclusion</h3> We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA levels to distinguish individuals with arthralgia who progress to clinical arthritis from non-progressors, especially applicable in ACPA+ individuals. The final model includes B cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model built in the ARRA cohort requires further validation in larger at-risk of RA cohorts. <h3>Acknowledgements</h3> Projects NU22-05-00226, MHCR-023728, SVV-260523 <h3>Disclosure of Interests</h3> None Declared.